Crucial cytokine interactions in nitric oxide production induced by Mycoplasma arthritidis superantigen.
Mycoplasma arthritidis causes autoimmune arthritis in rodents. It produces a superantigen (MAM) that simultaneously activates antigen presenting cells and T cells inducing nitric oxide and cytokine release. Nitric oxide is a key inducer and regulator of the immune system activation. Here, we investigated nitric oxide and cytokine production and interactions of these molecules in MAM-stimulated co-cultures of macrophages (J774A.1 cell line) with spleen lymphocytes. We found that: a) MAM-induced nitric oxide, interferon-gamma, membrane-associated tumor necrosis factor and interleukin-2 production in co-cultures of macrophages with lymphocytes from BALB/c and C3H/HePas but not from C57Bl/6 mice; b) production of nitric oxide was dependent on interferon-gamma whereas that of interferon-gamma was dependent on interleukin-2 and membrane-associated tumor necrosis factor; c) these cytokines up regulated MAM-induced nitric oxide production. Unraveling the mechanisms of cell activation induced by MAM might be helpful to design strategies to prevent immune system activation by superantigens and therefore in seeking amelioration of associated immunopathologies.
Shio
Marina Tiemi
MT
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1730, Cidade Universitária, São Paulo, SP, CEP: 05508-900, Brazil.
Olivier
Martin
M
Jancar
Sonia
S
Ribeiro-Dias
Fátima
F
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D045645:Mycoplasma arthritidis / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D016207:Cytokines; C052996:Mycoplasma arthritidis mitogen; D018089:Superantigens; D009569:Nitric Oxide